Marieke van Son

13 GENERAL INTRODUCTION AND THESIS OUTLINE Low-risk Intermediate-risk High-risk Active surveillance No PLND Active treatment (RP, RT) (Active surveillance) PLND at LNI risk >5% Active treatment (RP, RT) EBRT+6 months ADT +/-brachy boost PLND Active treatment (RP, RT) EBRT+36 months ADT +/-brachy boost RP +/-adjuvant RT or ADT Figure 4 – General treatment guidelines per prostate cancer risk group. PLND: pelvic lymph node dissection, RP: radical prostatectomy, RT: radiotherapy, LNI: lymph node involvement, ADT: androgen deprivation therapy. Image adapted from: The Sunshine Coast Urology Clinic (www.sunshinecoasturology.com.au ). Low- and favorable intermediate-risk patients are eligible for both surgery and radio- therapy, which carry equal but distinct risk-benefit profiles(56). However, as long-term observational cohort studies on (initial) conservative management have shown, the natural course of clinically localized disease is relatively mild, with cancer-specific survival rates of 80-90% after 10 years(57, 58). In an effort to reduce over-treatment of indolent non-lethal tumors, active surveillance (AS) has therefore emerged as the recommended strategy for patients with low-risk disease or highly selected favorable intermediate-risk patients (i.e. <10% Gleason pattern 4)(59, 60). In principle, AS is a de- ferred treatment strategy with curative intent, aiming to treat no earlier than necessary. To monitor the need for treatment, follow-up should at least include PSA-testing and DRE every 3-6 months, and standard repeat prostate biopsy after one year and every three years thereafter. PSA progression, clinical progression on DRE and/or radiological progression on mp-MRI (if performed) require interim repeat biopsy(61). This strict follow-up protocol is a downside of AS, with decreasing patient compliance over time, particularly regarding repeat biopsies(62). From a patient’s perspective, the burden of follow-up combined with fear of progressively growing cancer may favor immediate active treatment. Both AS and active treatment require a life expectancy of at least 10 years to expect any benefit from (potential) local treatment above a conservative watchful waiting strategy. Unfavorable intermediate- and high-risk patients require a more aggressive ap- proach, with a more extensive diagnostic evaluation (extended pelvic lymph node dissection [ePLND])(63) and use of multi-modal treatment, consisting of EBRT with systemic androgen deprivation therapy (ADT) and/or brachytherapy boost or RP with adjuvant radiotherapy to the prostate bed or ADT(24). Patients with ePLND-proven 1